Combined effects of avasimibe immunotherapy, doxorubicin chemotherapy, and metal–organic frameworks nanoparticles on breast cancer

Liu, Jun; Wang, Hongjian; Zhu, Delan; Wan, Yat-wah; Yin, Lei

doi:10.1002/jcp.29358

Cited by 38 publications

(25 citation statements)

References 37 publications

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“…Notably, although statins are well-known cholesterol-pathway inhibitors, they might target other pathways as well. For instance, statin treatment in various cancer cells leads to [126][127][128] Kras peptide vaccine, DC vaccine, anti-PD-1 + avasimibe…”

Section: Targeting Cholesterol Metabolism For Cancer Therapymentioning

confidence: 99%

Cholesterol metabolism in cancer: mechanisms and therapeutic opportunities

2020

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C holesterol is vital for the survival and growth of mammalian cells. More than a membrane constituent, cholesterol is a precursor to bile acids and steroid hormones, which can initiate or promote colon, breast and prostate cancers 1-3 . Cholesterol can also modulate signalling pathways involved in tumourigenesis and cancer progression by covalently modifying proteins including hedgehog and smoothened 4,5 , and by facilitating the formation of specialized membrane microdomains 6,7 . Brief overview of cholesterol metabolismEvery mammalian cell can synthesize cholesterol through the mevalonate pathway (Fig. 1a). Two acetyl-CoA molecules in the cytosol condense, thus forming acetoacetyl-CoA, which reacts with the third acetyl-CoA and yields 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). HMG-CoA is reduced to mevalonate by HMG-CoA reductase (HMGCR), the primary rate-limiting enzyme in cholesterol biosynthesis. A series of enzymatic reactions convert mevalonate to farnesyl pyrophosphate (FPP), a precursor of sterols and all non-sterol isoprenoids. The condensation of two FPP molecules to squalene commits the process to sterol production. FPP also gives rise to geranylgeranyl pyrophosphate (GGPP), and both FPP and GGPP can prenylate and activate several oncogenic proteins such as Ras 8 . Squalene is then oxidized by squalene epoxidase (SQLE) to 2,3-epoxysqualene, which is cyclized to lanosterol. In the next steps, lanosterol follows the Bloch pathway, the Kandutsch-Russell pathway or a hybrid pathway before it is finally converted to cholesterol.Beyond de novo cholesterol biosynthesis, most cells acquire cholesterol from low-density lipoprotein (LDL) taken up from the circulation via LDL receptor (LDLR)-mediated endocytosis 9 . Enterocytes absorb dietary cholesterol from the intestinal lumen in a process involving the cholesterol transporter NPC1L1, the clathrin adaptor NUMB and the adaptor protein LIMA1 (refs. 10-12 ). Cholesterol within the cell is dynamically transported, reaching the destined membranes for structural and functional needs 13 . Cholesterol in excess of the current cellular demand is either exported from the cell by ATP-binding cassette (ABC) transporters, Reprogrammed cholesterol metabolism in cancer cellsHallmark features of cancer cholesterol metabolism. As fastproliferating cells, cancer cells require high levels of cholesterol for membrane biogenesis and other functional needs. For example, the cholesterol-derived oncometabolite 6-oxo-cholestan-3β,5α-diol, which is enriched in patients with breast cancer, binds glucocorticoid receptors and subsequently promotes tumour growth 19 . In general, cholesterol metabolism substantially contributes to cancer progression, including cell proliferation, migration and invasion 20-23 .Cholesterol metabolism produces essential membrane components as well as metabolites with a variety of biological functions. In the tumour microenvironment, cell-intrinsic and cell-extrinsic cues reprogram cholesterol metabolism and consequently promote tumourigenesis. Cholesterol-de...

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Section: Targeting Cholesterol Metabolism For Cancer Therapymentioning

confidence: 99%

Cholesterol metabolism in cancer: mechanisms and therapeutic opportunities

2020

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“…There are a significant number of studies describing the delivery of Dox by a diverse range of MOFs—it is likely the most commonly used drug molecule in this area—and it has allowed exemplification of strategies such as targeted tumor uptake, 34 , 35 stimuli-responsive release, 36 , 37 multimodal treatments, 38 , 39 and theranostics. 40 , 41 A large number of these reports focus on the delivery of Dox from nanoparticles and composites of ZIF-8, 34 , 38 , 39 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 in which tetrahedral Zn 2+ centers connect 2-methylimidazolate linkers into a sod net, 51 and UiO-66, 34 , 35 , 52 , 53 , 54 in which Zr 6 O 4 (OH) 4 (RCO 2 ) 12 secondary building units (SBUs) connect 1,4-benzenedicarboxylate (BDC) linkers into a fcu net. 55 In both cases, the small pore apertures—3.4 Å for ZIF-8 (up to 12.0 Å when flexibility 56 , 57 is taken into account) and 6.0 Å for UiO-66—seemingly preclude penetration of the Dox molecule, which has a maximum diameter of 15.4 Å, 58 into the porosity of the MOF.…”

Section: Introductionmentioning

confidence: 99%

“… 55 In both cases, the small pore apertures—3.4 Å for ZIF-8 (up to 12.0 Å when flexibility 56 , 57 is taken into account) and 6.0 Å for UiO-66—seemingly preclude penetration of the Dox molecule, which has a maximum diameter of 15.4 Å, 58 into the porosity of the MOF. While some reports describe in situ encapsulation of Dox during the synthesis of these smaller-pore MOFs, 38 , 39 , 42 , 43 the size disparity suggests it would be bound on external particle surfaces if loaded postsynthetically, which should modify release mechanisms. The localization of Dox on MOF nanoparticle surfaces would also have a significant impact on external surface modifications, which are often used to induce targeting or stimuli-responsive release mechanisms, but this is rarely discussed.…”

Section: Introductionmentioning

confidence: 99%

Identifying Differing Intracellular Cargo Release Mechanisms by Monitoring In Vitro Drug Delivery from MOFs in Real Time

Μαρκοπούλου

Panagiotou

et al. 2020

Cell Reports Physical Science

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“…Through EPR, nanocarriers have enhanced the anticancer effects of PTX and DOX, since nanocarriers can passively enter cancer cells and act on intracellular targets [ 165 ]. In the latest study, DOX is loaded into the zeolitic imidazolate framework, leading to effective drug accumulation in tumors due to the EPR effect and precise release of the drug in the tumor site by its pH sensitive instability with no side effects to the normal tissue [ 114 ].…”

Section: Application and Clinical Trials Of Nanocarrier-based Thermentioning

confidence: 99%

Recent Progress of Nanocarrier-Based Therapy for Solid Malignancies

Wei

Lau

2020

Cancers

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Conventional chemotherapy is still an important option of cancer treatment, but it has poor cell selectivity, severe side effects, and drug resistance. Utilizing nanoparticles (NPs) to improve the therapeutic effect of chemotherapeutic drugs has been highlighted in recent years. Nanotechnology dramatically changed the face of oncology by high loading capacity, less toxicity, targeted delivery of drugs, increased uptake to target sites, and optimized pharmacokinetic patterns of traditional drugs. At present, research is being envisaged in the field of novel nano-pharmaceutical design, such as liposome, polymer NPs, bio-NPs, and inorganic NPs, so as to make chemotherapy effective and long-lasting. Till now, a number of studies have been conducted using a wide range of nanocarriers for the treatment of solid tumors including lung, breast, pancreas, brain, and liver. To provide a reference for the further application of chemodrug-loaded nanoformulations, this review gives an overview of the recent development of nanocarriers, and the updated status of their use in the treatment of several solid tumors.

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Combined effects of avasimibe immunotherapy, doxorubicin chemotherapy, and metal–organic frameworks nanoparticles on breast cancer

Cited by 38 publications

References 37 publications

Cholesterol metabolism in cancer: mechanisms and therapeutic opportunities

Cholesterol metabolism in cancer: mechanisms and therapeutic opportunities

Identifying Differing Intracellular Cargo Release Mechanisms by Monitoring In Vitro Drug Delivery from MOFs in Real Time

Recent Progress of Nanocarrier-Based Therapy for Solid Malignancies

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